Immunogens inducing protective, disease-sparing CD8+ T cell responses are a primary focus of research efforts at the VRC. These studies are designed to identify interventions that will increase the efficiency of nucleic acid and vector-based immunization and to optimize the conditions of each intervention. The magnitude and the quality of the immune responses induced by each vector will be compared using murine prime-challenge models. The RSV F glycoprotein is a key target for vaccine-induced neutralizing antibody. Our hypothesis is that understanding the mechanism of antibody neutralization will be facilitated by defining the structure of F and the structure of epitopes associated with neutralization. This will allow novel antigen design. Characterizing the chemistry and post-translational modifications in F will also promote improved vaccine antigen design.